Neuron type‐specific effects of brain‐derived neurotrophic factor in rat superficial dorsal horn and their relevance to ‘central sensitization’
Bibliographic record
Abstract
Chronic constriction injury (CCI) of the rat sciatic nerve increases the excitability of the spinal dorsal horn. This 'central sensitization' leads to pain behaviours analogous to human neuropathic pain. We have established that CCI increases excitatory synaptic drive to putative excitatory, 'delay' firing neurons in the substantia gelatinosa but attenuates that to putative inhibitory, 'tonic' firing neurons. Here, we use a defined-medium organotypic culture (DMOTC) system to investigate the long-term actions of brain-derived neurotrophic factor (BDNF) as a possible instigator of these changes. The age of the cultures and their 5-6 day exposure to BDNF paralleled the protocol used for CCI in vivo. Effects of BDNF (200 ng ml(-1)) in DMOTC were reminiscent of those seen with CCI in vivo. These included decreased synaptic drive to 'tonic' neurons and increased synaptic drive to 'delay' neurons with only small effects on their membrane excitability. Actions of BDNF on 'delay' neurons were exclusively presynaptic and involved increased mEPSC frequency and amplitude without changes in the function of postsynaptic AMPA receptors. By contrast, BDNF exerted both pre- and postsynaptic actions on 'tonic' cells; mEPSC frequency and amplitude were decreased and the decay time constant reduced by 35%. These selective and differential actions of BDNF on excitatory and inhibitory neurons contributed to a global increase in dorsal horn network excitability as assessed by the amplitude of depolarization-induced increases in intracellular Ca(2+). Such changes and their underlying cellular mechanisms are likely to contribute to CCI-induced 'central sensitization' and hence to the onset of neuropathic pain.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".